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Article: Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells

TitlePoly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells
Authors
Issue Date2010
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/
Citation
Bmc Cancer, 2010, v. 10 How to Cite?
AbstractBackground: There is increasing evidence that the toll-like receptor 3 (TLR3) is an interesting target for anti-cancer therapy. Unfortunately, most laboratory investigations about the impact of TLR3 stimulation on human malignant cells have been performed with very high concentrations - 5 to 100 μg/ml - of the prototype TLR3 ligand, poly(I:C). In a previous study focused on a specific type of human carcinoma - nasopharyngeal carcinoma - we have shown that concentrations of poly(I:C) as low as 100 ng/ml are sufficient to induce apoptosis of malignant cells when combined to a pharmacological antagonist of the IAP family based on Smac mimicry.Methods: This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types.Results: We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines.Conclusions: Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas. © 2010 Friboulet et al; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/124492
ISSN
2015 Impact Factor: 3.265
2015 SCImago Journal Rankings: 1.627
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Ligue Nationale contre le Cancer (comites d'ile de France)
Agence Nationale de la Recherche (EBV-inter)
Funding Information:

This study was supported by grants from the Ligue Nationale contre le Cancer (comites d'ile de France) and the Agence Nationale de la Recherche (EBV-inter). We thank Xiaodong Wang, Lin Li and Patrick Harran for generously providing RMT 5265 and HS 4404.

References

 

DC FieldValueLanguage
dc.contributor.authorFriboulet, Len_HK
dc.contributor.authorGourzones, Cen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorMorel, Yen_HK
dc.contributor.authorPaturel, Cen_HK
dc.contributor.authorTémam, Sen_HK
dc.contributor.authorUzan, Cen_HK
dc.contributor.authorBusson, Pen_HK
dc.date.accessioned2010-10-31T10:37:26Z-
dc.date.available2010-10-31T10:37:26Z-
dc.date.issued2010en_HK
dc.identifier.citationBmc Cancer, 2010, v. 10en_HK
dc.identifier.issn1471-2407en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124492-
dc.description.abstractBackground: There is increasing evidence that the toll-like receptor 3 (TLR3) is an interesting target for anti-cancer therapy. Unfortunately, most laboratory investigations about the impact of TLR3 stimulation on human malignant cells have been performed with very high concentrations - 5 to 100 μg/ml - of the prototype TLR3 ligand, poly(I:C). In a previous study focused on a specific type of human carcinoma - nasopharyngeal carcinoma - we have shown that concentrations of poly(I:C) as low as 100 ng/ml are sufficient to induce apoptosis of malignant cells when combined to a pharmacological antagonist of the IAP family based on Smac mimicry.Methods: This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types.Results: We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines.Conclusions: Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas. © 2010 Friboulet et al; licensee BioMed Central Ltd.en_HK
dc.languageengen_HK
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/en_HK
dc.relation.ispartofBMC Canceren_HK
dc.rightsB M C Cancer. Copyright © BioMed Central Ltd.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAdaptor Proteins, Vesicular Transport - metabolism-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols - pharmacology-
dc.subject.meshApoptosis - drug effects-
dc.subject.meshInhibitor of Apoptosis Proteins - antagonists and inhibitors - genetics - metabolism-
dc.subject.meshNeoplasms - genetics - metabolism - pathology-
dc.titlePoly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1471-2407&volume=10&issue=327&spage=&epage=&date=2010&atitle=Poly(I:C)+induces+intense+expression+of+c-IAP2+and+cooperates+with+an+IAP+inhibitor+in+induction+of+apoptosis+in+cancer+cells-
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1471-2407-10-327en_HK
dc.identifier.pmid20576118-
dc.identifier.pmcidPMC2928000-
dc.identifier.scopuseid_2-s2.0-77954856721en_HK
dc.identifier.hkuros182820en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954856721&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue327-
dc.identifier.isiWOS:000280358000001-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridFriboulet, L=25640560500en_HK
dc.identifier.scopusauthoridGourzones, C=21740577000en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridMorel, Y=7005872527en_HK
dc.identifier.scopusauthoridPaturel, C=19035771800en_HK
dc.identifier.scopusauthoridTémam, S=6602890744en_HK
dc.identifier.scopusauthoridUzan, C=22837114200en_HK
dc.identifier.scopusauthoridBusson, P=7005088091en_HK

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